Early Use of Long-acting Tacrolimus in Lung Transplant Recipients
Status:
Not yet recruiting
Trial end date:
2022-08-01
Target enrollment:
Participant gender:
Summary
Lung transplantation is a life-saving therapy for patients with advanced lung disease,
however, necessitates the use of life-long immunosuppressive therapy for the prevention of
acute and chronic rejection. The backbone of immunosuppression is the calcineurin-inhibitor
class, with tacrolimus being the preferred drug due to its potency and improved side-effect
profile. Nevertheless, tacrolimus is associated with several side effects including increased
risk for infection and malignancy, tremors, headaches, seizures, hypertension, leukopenia and
renal dysfunction. In fact, by 6 months post-transplant, 50% of patients will have a 50%
decline in eGFR and by 5 years post-transplant ~10% of patients will have advanced renal
disease that may require renal replacement therapy and/or kidney transplantation. Tacrolimus
induces a nephropathy in two ways- acute calcineurin inhibitor nephrotoxicity (CIN) is
mediated by afferent arteriolar vasoconstriction, whereas chronic CIN is due to interstitial
nephritis and fibrosis. Immunosuppressive regimens that spare or dose-reduce calcineurin
inhibitors have been shown to have a modest impact on preserving renal function, but are
limited by timing. Although most studies support implementing renal preserving protocols
early on, this is balanced by the potential for acute cellular rejection, antibody mediated
rejection and anastomotic dehiscence.
Long-acting Tacrolimus (LCP-tacrolimus) may have the potential to bridge the balance of
providing potent immunosuppression, while sparing renal function, due to the better systemic
dose levels and improved concentration/dose ration achieved with it compared to
IR-tacrolimus, evidenced in the renal transplant population. There is limited experience with
LCP-tacrolimus in lung transplantation. Several case reports chronicling the late conversion
from IR-tacrolimus to LCP-tacrolimus due to absorption issues or side-effect intolerance,
have demonstrated safety and tolerability. The investigators seek to determine whether early
use of LCP-tacrolimus in lung transplant recipients following the index hospitalization is
acceptable, and propose a single-center prospective, randomized, controlled pilot study of
early-use LCP-tacrolimus in lung transplant recipients to assess safety, tolerability and
side-effects of LCP-tacrolimus.